Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

IntroductionIn Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug‐resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015.MethodsThe HIV threshold survey methodology (HIV‐THS, WHO) targeting antiretroviral‐naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing.ResultsWe analysed samples from 1568 antiretroviral‐naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor‐specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails.ConclusionsTo the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.

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Propofol, which is widely used as an intravenous anesthetic, has a phenolic structure similar to that of α-tocopherol with antioxidant properties that could prevent genotoxicity and cytotoxicity in lymphocytes of anesthetized patients. The aims of this study were to evaluate oxidative DNA damage and apoptosis in lymphocytes and the expression of DNA repair genes in blood cells from patients undergoing elective surgery under anesthesia with propofol. Twenty healthy adults of both genders (18-50 years old) who were scheduled for otorhinological surgery were enrolled in this study. Blood samples were collected before anesthesia induction (T₁-baseline), 120 min after anesthesia induction (T₂), and on the first postoperative day (T₃). Oxidative DNA damage in peripheral lymphocytes was assessed using the comet assay. Lymphocytes were phenotyped as T helper or cytotoxic T cells, and apoptosis was evaluated using flow cytometry. The expression of DNA repair genes (hOGG1 and XRCC1) was assessed by quantitative polymerase chain reaction. A reduction in the level of oxidized purines in DNA (P < 0.01) was observed 120 min after anesthesia induction, and reduced apoptosis of T helper cells was observed 120 min after anesthesia induction and on the first postoperative day. Down-regulation of hOGG1 and XRCC1 gene expression was observed on the first postoperative day. In conclusion, patients undergoing non-invasive surgery under propofol anesthesia presented lower levels of oxidized purines and apoptosis of T helper lymphocytes. Furthermore, anesthesia with propofol did not directly influence the expression of the DNA repair genes hOGG1 and XRCC1 in blood cells.

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Devido à similaridade nas rotas de transmissão, a co-infecção HIV/HCV é freqüente, afetando em média 30 a 50% dos portadores de HIV. O presente estudo visou avaliar uma possível associação entre os subtipos do HIV e genótipos do HCV em pacientes co-infectados, com base na análise das freqüências em pacientes mono e co-infectados. Para determinação da freqüência dos subtipos HIV e genótipos HCV, foram analisados respectivamente 124 e 496 pacientes mono-infectados. O estudo da co-infecção foi realizado num grupo de 150 pacientes HIV positivos e esteve presente em 22 (14,7%) dos pacientes. A freqüência dos subtipos do HIV-1 em mono-infectados foi: subtipo B (85,5%), subtipo F (12,9%) e recombinante B/F (1,6%), enquanto nos genótipos HCV foi: 1a (25%), 1b (29,4%), 1a/1b (3,6%), 3a (35%), 2 (1,8%) e 5 (0,4%). Nos co-infectados o padrão de distribuição dos subtipos HIV-1 é semelhante aos mono-infectados, ou seja, subtipo B (85,0%), seguido do subtipo F (15,0%). A distribuição de freqüência de genótipos HCV nos co-infectados foi: 1a (36,3%), 1b (27,3%), 1a/1b (9,1%) e 3a (27,3%) mostrando um aumento de 10% na freqüência do genótipo 1, queda de 7,7% no genótipo 3 e ausência de outros genótipos. A análise estatística de associação entre os subtipos HIV e genótipos HCV (Goodman) mostrou que no genótipo 1 (HCV) ocorreu predominância do subtipo B, enquanto no genótipo 3 (HCV) a distribuição dos subtipos B e F (HIV-1) foi casual. Isto aponta para a necessidade de mais estudos desse grupo e um maior valor amostral.

Alterations in the methylation status of genes may contribute to the progression of Chronic Myeloid Leukemia (CML). In this study, the methylation status in exon2 of SOCS-1 and promoter regions of both SOCS-1 and JUNB were evaluated in CML patients. The methylation status of these genes was analyzed using methylation-specific Polymerase Chain Reaction (MSP) in 30 samples from CML patients, 30 samples from these same patients after hematopoietic stem cell transplantation (HSCT) and 30 samples from healthy controls. The samples of CML patients presented methylation as follows: JUNB gene (3.3%), promoter region of the SOCS-1 gene (6.6%) and exon2 of the SOCS-1 gene (46.6%). The samples of the healthy individuals presented methylation (10%, P = 0.002) only in exon 2 of the SOCS-1 gene. After transplantation, patients presented alterations in the methylation status of the promoter region of the SOCS-1 gene (6.6%), exon2 of SOCS-1 (46.6%) and the promoter region of the JUNB gene (16.6%). Methylation of the promoter regions of the SOCS-1 gene and the JUNB gene is not a frequent event in CML. In contrast, SOCS-1 gene methylation in exon2 is a frequent event, susceptible to alterations in status after HSCT with possible implications for the progression of this disease.

Background: The rates of Helicobacter pylori infection are very high worldwide, but only a minority of infected patients develop gastric carcinoma. This might be related, among several factors, to the colonization of the human stomach by pathogenic Helicobacter pylori strains. Objective: To investigate the distribution of cagA and vacA genotypes of Helicobacter pylori in paraffin-embedded gastric samples from patients with gastric cancer. Material and methods: Paraffin-embedded samples from 42 patients with gastric cancer were histologically examined and evaluated by PCR for H. pylori cagA and vacA (s and m regions) genotypes. Results: Histological analysis allowed direct visualization of H. pylori in 85.7% of cases and PCR for urease C gene detected H. pylori in 95% of cases. The presence of cagA gene was detected in 23 (54.7%) patients with gastric cancer. The s1 allele from vacA gene was found in samples from 24 (57.1%) patients and the m1 allele in 26 (61.9 %). The s1m1 genotype was detected in 24 (57.1%) patients with gastric cancer. The s2 allele was found in samples from four patients (9.5%) and the m2 allele in three (7.1%) patients. The distribution of H. pylori genotypes was similar in both intestinal and diffuse types of gastric carcinoma. Conclusion: Our results confirm the relevance of the pathogenic cagA and vacA H. pylori genotypes for significant organic lesions, such as gastric cancer, suggesting a possible role for H. pylori in the pathogenesis of gastric carcinoma. Helicobacter pylori Gastric cancer cagA vacA J Bras Patol Med Lab • v. 42 • n. 1 • p. 25-30 • fevereiro 2006 ARTIgO ORIgINAL ORIgInal papER Primeira submissão em 29/09/05 Última submissão em 21/12/05 Aceito para publicação em 11/01/06